Accelerated cognitive decline and hippocampal volume loss in mild cognitive impaired carriers of Apolipoprotein‐E ε4

Abstract

AbstractBackgroundThe ε4 allele of the Apolipoprotein‐E (APOE) gene is the major genetic risk factor for late‐onset Alzheimer’s disease (AD). APOE ε4 carriers represent around 45% of AD population, with each copy of APOE ε4 allele conferring increased risk for AD. Here, we aim to quantify disease progression during the early clinical stage of AD using imaging biomarkers to stratify patient populations for therapeutic interventions.MethodsData used in the preparation of this abstract were obtained from the Alzheimer’s Disease Neuroimaging Initiative. CDR some of boxes (CDR‐SB), PET (amyloid load; Florbetapir), MRI (hippocampal volume) and APOE4 genotype were collected. Only MCI patients were included (MMSE=27.6±1.8 and global‐CDR=0.5±0.05). Available follow up data with at least 10 participants were included in the analysis.ResultsData from 1021 participants with baseline MCI status were included in the study (110 ε4 homozygotes, 397 heterozygotes ε4).At baseline, CDR‐SB of non‐carriers and ε4 homozygotes was not different (p=0.24). The annual rate of cognitive decline in ε4 homozygotes (0.7 points per year; p=7e‐8) and heterozygotes ε4 (0.56 points per year; p=4e‐8) was 3.7 to 4.6 times greater than non‐carriers (0.15 points per year; p=0.00005).At baseline, hippocampal volume was significantly (p<0.01) lower in ε4 homozygotes (6.50 mL) and heterozygotes ε4 (6.76 mL) compared to non‐carriers (6.98 mL). The annual rate of hippocampal loss in ε4 homozygotes (0.09 mL; p=0.032) and heterozygotes ε4 (0.13 mL; p=0.0006) was faster than non‐carriers (0.03 mL; p=0.16).At baseline, amyloid load was significantly (p<0.0001) higher in ε4 homozygotes (SUVR=1.37) and heterozygotes ε4 (SUVR=1.31) compared to non‐carriers (SUVR=1.13). The rates of progression were not significantly different across groups.ConclusionAPOE ε4 carriers showed notably greater rate of progression on CDR‐SB compared to non‐carriers. Greater amyloid load and hippocampal atrophy were observed in APOE ε4 carriers compared to non‐carriers at baseline although the CDR‐SB scores were comparable. The amyloid deposition appeared to plateau at MCI. Hippocampal volume loss continued in all groups, with a fastest progression rate in ε4 carriers. Result suggests that detection of therapeutic changes from interventions may be more efficient in this population than the broader population of MCI patients.